In the pharmaceutical industry, tablets appear to be the most advantageous form for the administration of a drug. Packaging and handling are normal operations onto which pharmaceutical products are submitted, which makes tablets the preferred choice. Additionally, tablets are frequently employed in non pharmaceutical fields such as fish foods, plant growth regulators, pesticides, herbicides and the like.
These tablets must show good mechanical qualities in view of the manufacturing process involved and the subsequent handling and packaging. The most important mechanical properties are the hardness and the resistance to friability. These features are closely related to one another since an increase in tablet hardness generally leads to a decrease in tablet friability. The term hardness describes the resistance of the tablet to stresses and strains of transportation and storage. Usually, one measures the crushing-strength defined as "that compressional force which, when applied diametrically to a tablet, just fractures it" (Brook et al. J. Pharm. Sci., 1968, 57, 481-484). If the hardness of the tablet is insufficient i.e. when the crushing-strength value is too low, tablets are likely to break, especially during handling when they are subjected to repeated shocks. Furthermore, excessive friability may cause dusting and crumbling of the tablet, resulting in a diminution in active ingredient dosage and in a poor appearance of the tablet.
Thus, the manufacture of tablets involves the optimization of these two characteristics. If a quick release of the drug is desired, then the tablet must also possess acceptable disintegration characteristics both in vivo and in vitro.
The simplest and most economical procedure for the manufacturing of tablets is the direct compression of all the ingredients distributed homogeneously. The procedure i.e. the powder compression in a tablet puncher follows directly the dry blending of one or more active ingredients and at least one of the following: filler, binder, disintegrant and lubricant, and the like.
Materials such as sodium chloride, saccharose, salicylamide, hexamethylenetetramine and the like are readily directly compressed alone in dry form into a coherent and compact mass in a conventional tablet puncher. However, the majority of active ingredients require a binding agent to maintain the drug particles together in a tablet. Such binding agent increases the strength of the compressed tablet and decreases its friability, leading to an improvement in the tablet appearance and mechanical characteristics. An appropriate binding agent possesses flowing properties, can be blended easily and is inert and non-toxic. Conventional binders currently in use include: microcrystalline cellulose (Avicel PH-101.TM. and PH-102.TM.) polyvinylpyrrolidone (Kollidon.TM., Plasdone.TM.), cornstarch, wheat starch, potato starch, modified starches, gums, and the like. All these products are usually employed in direct compression at a minimum concentration level of 20%.
Disintegration rate is important when the tablet is contacted with fluids such as body fluids. Tablets should immediately fall apart into distinct particles whenever the drug is to be released very quickly. They must disintegrate rapidly enough to provide adequate blood levels of drug.
If quick disintegration of the tablet is required, disintegrants are added. A effective disintegrated is an agent that promotes destruction of the tablet physical integrity. Typical disintegrants are: corn starch, gelatinized starches (Sta Rx.TM.), modified starches e.g. sodium starch glycolate (Primojel.TM.).
Co-pending application U.S. Ser. No. 787,721 filed Oct. 31, 1991 discloses cross-linked amylose having a cross-linking degree of 1 to 10, which possesses controlled release properties when mixed with a pharmaceutical product. However, such controlled release properties are observed only if the amount of cross-linked amylose is above 40% by weight in the tablet.
Short et al. (U.S. Pat. No. 3,622,677) discloses a binder/disintegrant constituted of modified and/or cross-linked starch. However, the binding properties of their materials are considerably low, which means that a significant amount of the binder needs to be present in the tablet.
Trubiano (U.S. Pat. No. 4,369,308) describes modified starches for use as disintegrant. These starches however have poor binding properties.
Some materials, for example microcrystalline cellulose (Avicel PH 101.TM. and Avicel PH 102.TM.) present binding and disintegrating characteristics of both binders and disintegrants. Despite the existence of many binders and disintegrants, pharmaceutical researchers have continued their efforts to develop improved materials capable of being employed as a binder and/or as a disintegrant in the preparation of tablets by direct compression.